a study of wxfl10030390 in patients with advanced solid tumors or lymphoma

Conditions: Advanced Cancer

Summary: wxfl10030390 (wx390) is a novel oral small molecular that inhibits phosphoinositide-3 kinase (pi3k) and mammalian target of rapamycin (mtor) and has demonstrated potent inhibitory effects on multiple human tumor xenografts. the first-in-human study is conducted to assess the maximum tolerated dose (mtd) and dose-limiting toxicity (dlt), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of wx390 at single dose and multiple doses.

this study will be an open-lable, phase ⅰ study and will evaluate the safety and pharmacokinetics of wx390 after a single administration followed by a 28-day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-lable administration of wx390 at the mtd.

Eligibility criteria:
inclusion criteria: * ≥18 and ≤75 years of age * histological or cytological confirmed advanced solid tumor or lymphoma, standard regimen failed or no standard regimen available * eastern cooperative oncology group (ecog) performance status of 0-1 * life expectancy of more than 3 months * at least one measurable lesion according to recist 1.1 or lugano 2014 * adequate organic function: absolute neutrophil count (anc) ≥2.0×109/l，plt≥100×109/l，hb≥9g/l hepatic function:tbil≤1.5×upper limit of normal (uln)，alanine aminotransferase (alt) ≤2.5×uln，aspartate aminotransferase (ast) ≤2.5×uln; renal function:cr≤1.5×uln and\>50ml/min; coagulation function: aptt≤1.5 ×uln，pt≤1.5 ×uln, inr≤1.5 ×uln; glu\<7mmol/l and hba1c\<7%; tg≤1.5×uln，chol≤1.5×uln * subjects who have the fertility should agree to use reliable contraceptive methods during this study and subsequently at least 12 weeks after the last administration; for female subjects, the blood pregnancy test should be negative within 7 days prior to the enrollment * signed and dated informed consent exclusion criteria: * anti-cancer therapy within 4 weeks prior to the initiation of investigational treatment * surgery within 4 weeks prior to the initiation of study treatment * use of strong inducers or inhibitors of cyp3a4 within 1 weeks before the first dose of study treatment. see appendix 5 for a list of such medications * received corticosteroids treatment or other immunodepressant within 2 weeks before the first dose of study treatment * toxicity from a previous anti-tumor treatment that does not return to grade 0 or 1 (except for alopecia) * patients with clinical symptomatic brain metastases, spinal compression, meningitis carcinomatosa or other evidence that shows uncontrolled brain or spinal metastases * previous treatment with pi3k/mtor inhibitors * patients who once or being suffer interstitial lung disease * evidence of ongoing or active infection * history of human immunodeficiency virus (hiv) infection * history of hepatitis b or c infection * clinically significant cardiovascular disease, including but not limited to acute coronary syndrome, congestive heart-failure, cerebral stroke within 6 months prior to enrollment, new york heart association class ≥ii cardiac functional grading or left ventricular ejection fraction (lvef) \< 50% * inability to take medication orally * severe gastrointestinal disease leading to diarrhea * diabetics receiving insulin treatment * patients with active autoimmune disease (including systemic lupus erythematosus, rheumatoid arthritis, nodular vasculitis) * abuse of alcohol or drugs * people with cognitive and psychological abnormality or with low compliance * pregnant or lactating women * researchers believe that subjects may not be able to complete the study or may not be able to comply with the requirements of this study

Keywords: phosphoinositide-3 kinase (pi3k) mammalian target of rapamycin (mtor)